Safety, Tolerability and Pharmacokinetics of Repeat Doses of GSK1014802.

Single-blind, Randomised, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Repeat Doses of GSK1014802 and Its Interaction With Food in Healthy Volunteers

GSK1014802 is a use-dependent sodium channel blocker and an effective anticonvulsant in animal models.

This study is being conducted to obtain information regarding the safety, tolerability and pharmacokinetics of repeated doses of GSK1014802 administered for up to 28 days in healthy male or female subjects. In addition, the effect of food on the pharmacokinetics of GSK1014802 will be investigated.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Bipolar Depression
• Intervention / Treatment: Drug: Placebo; Drug: GSK1014802

Detailed Description

This study, previously posted by GlaxoSmithKline (GSK), was transitioned to Convergence Pharmaceuticals, Ltd., which spun off from GSK. Convergence Pharmaceuticals, Ltd., has now been acquired by Biogen.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

  • Male or female (of non-child bearing potential) subjects aged between 18 and 55 years.
  • A female subject is eligible to participate if she is of non-childbearing potential.
  • Male subjects must agree to use an acceptable form of contraception.
  • Body weight ≥ 50 kg and BMI within the range 19 - 29.9 kg/m2 (inclusive)
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

• The subject has a positive pre-study drug/alcohol screen.

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive test for HIV antibody.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females).
  • Current or past history of symptomatic orthostatic hypotension or history of unexplained vasovagal episode(s).
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives (60 h) or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Pregnant females.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • . Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  • History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1	Drug: Placebo; Tablets to match GSK1014802; Drug: GSK1014802; Sodium channel blocker; Other Names: BIIB074 and CNV1014802
Other: Cohort 2	Drug: Placebo; Tablets to match GSK1014802; Drug: GSK1014802; Sodium channel blocker; Other Names: BIIB074 and CNV1014802
Other: Cohort 3	Drug: Placebo; Tablets to match GSK1014802; Drug: GSK1014802; Sodium channel blocker; Other Names: BIIB074 and CNV1014802
Other: Cohort 4	Drug: Placebo; Tablets to match GSK1014802; Drug: GSK1014802; Sodium channel blocker; Other Names: BIIB074 and CNV1014802

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability will be evaluated by monitoring AEs and concomitant medication, ECG, Lead II monitoring, Holter monitoring, vital signs, and laboratory parameters.	14-28 days
Blood concentrations of GSK1014802 following a single oral dose of GSK1014802.	1 day
Blood concentrations of GSK1014802 following repeated oral doses of GSK1014802 given once daily or twice daily and their relationship with the GSK1014802 exposure after a single dose.	14-28 days
Blood concentrations of GSK1014802 following repeated oral doses of GSK1014802 given once daily with or without food.	14-28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Bond-Lader VAS scale	14-28 days

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Biogen Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2008
• Primary Completion (Actual): December 31, 2008
• Study Completion (Actual): December 31, 2008

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 21, 2009
• First Posted (Estimate): May 25, 2009

Study Record Updates

• Last Update Posted (Actual): October 30, 2017
• Last Update Submitted That Met QC Criteria: October 27, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: bipolar disorder; repeat dose; sodium channel blocker
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: 107727; SCB107727